Ly Thi Huong Nguyen1, Sang-Hyun Ahn2, Uy Thai Nguyen1, In-Jun Yang3. 1. Department of Physiology, College of Korean Medicine Dongguk University, Gyeongju 38066, Republic of Korea. 2. Department of Anatomy, College of Korean Medicine Semyung University, Jecheon 27136, Republic of Korea. 3. Department of Physiology, College of Korean Medicine Dongguk University, Gyeongju 38066, Republic of Korea. Electronic address: injuny@dongguk.ac.kr.
Abstract
BACKGROUND: The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms. METHODS: An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an in vitro model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells. RESULTS: Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells. CONCLUSION: These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.
BACKGROUND: The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms. METHODS: An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an in vitro model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells. RESULTS: Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells. CONCLUSION: These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.
Authors: Rodrigo Boscariol; Érika A Caetano; Denise Grotto; Raquel M Rosa-Castro; José M Oliveira Junior; Marta M D C Vila; Victor M Balcão Journal: Pharmaceutics Date: 2022-04-02 Impact factor: 6.525